Stimulation delays Huntington's dementia

Source: Howard Florey Institute

Scientists at Melbourne's Howard Florey Institute have discovered that mental and physical stimulation delays the onset of dementia in Huntington's disease-affected mice.

Drs Jess Nithianantharajah and Anthony Hannan showed that by providing the transgenic mice with an enriched environment that enhanced their mental and physical stimulation, the mice performed better on memory tests.

The mice initially showed deficits in short-term hippocampal-dependent memory prior to the onset of motor symptoms, as is observed in human Huntington's patients.

The provision of an enriched physical and mental environment, however, "significantly ameliorated" this memory deficiency, the researchers say.

She said the team had also showed that specific molecular changes were noticed in the synapses of the HD mice, suggesting that these changes may contribute to the cognitive alterations observed.

"The Huntington's disease mice without increased mental and physical activity showed decreased levels of specific proteins that are expressed at the synapse, which are essential for normal brain function," she said.

"But the Huntington's disease mice exposed to increased mental and physical activity did not show this decrease."

The researchers found through analysis of the synaptophysin protein that environmental enrichment increased synaptophysin levels in the frontal cortex and hippocampus in both wild-type and HD mice.

In comparison, they write, an analysis of postsynaptic proteins revealed that HD animals show decreased levels of PSD-95 and GluR1 (two important synaptic membrane proteins), but no change in levels of gephyrin (a scaffold protein).

"Furthermore, at 12 weeks of age when we observe a beneficial effect of enrichment on spatial learning in HD mice, enrichment also delays the onset of a deficit in hippocampal PSD-95 levels," they write.

The research was recently published online in the journal Neurobiology of Disease and involved collaborations between the Howard Florey Institute and the University of Melbourne.